Substantially monostatic, substantially confocal optical systems for examination of samples

ABSTRACT

The present invention relates to systems and methods for examining a sample using a substantially monostatic, substantially confocal optical system comprising transmitting optics that focus an illuminating light upon the sample and receiving optics that collect light emitted from the sample following illumination thereof. In certain embodiments, the receiving optics may be arranged circumferentially around the light path traversed by the illuminating light. In certain embodiments, video apparatus may be included to produce images or to align the system in proximity to the target tissue. The systems and methods of the present invention may be directed towards the examination of a body tissue to provide a medical diagnosis.

This application claims priority to U.S. Provisional Patent Application60/113,761 filed Dec. 23, 1998.

FIELD OF THE INVENTION

This invention relates to the delivery of excitation light to a targettissue and the collection of response light therefrom for spectralanalysis.

BACKGROUND OF THE INVENTION

Optical methods are being used with increasing frequency to determinethe composition and state of samples. In particular, the use of opticaltechniques is growing in the medical arts for the diagnosis of tissuehealth in-vivo. In some instances, a beam of light is used to illuminatethe tissue in a specific region, causing excitation of said tissue.Light emitted by the tissue is then collected by the receiving deviceand analyzed to determine the physical health of the tissue.

Two methods are known in the art that deliver and receive illuminationfrom a designed region of tissue. In the first method, termed bistatic,the illuminating beam is focused on the sample from one direction, andlight that is backscattered or emitted from the sample is received by anoptical system located in a position different from the position of thedelivery system. In the second method, termed monostatic, theilluminating beam path and the receiver beam path lie along the sameline of sight. Such an optical scheme is also called confocal if thelocation of the sample is at the focal point of both the illuminationoptical system and the receiver optical system of the device.

According to the bistatic method for examining a sample, the field ofillumination from the source and the field of view of the receiver arealigned so as to overlap at the sample, while illumination and viewingtake place at different locations. Certain limitations are understood toaccompany bistatic methods. For example, when this method is employedwith an illuminating device that does not directly contact the sample,it is sensitive to misalignments of the device to the sample, so thatany error in the distance of the non-contact device from the tissue mayresult in significant decrease in the amount of light collected by thereceiver.

Bistatic optical probes may have illumination and receiving sectionssufficiently separated from each other that the optical paths from thesample to each section are oriented along different directions. Theeffect of this optical design is that the illumination path and thereceiving path form two sides of a triangle, intersecting in a singlelocalized region. The surface of the sample may then be positioned inthis overlap region. For some applications, this triangulation can beexploited. The receiver section may be configured to collect a signalonly when the proper distance from the probe to the sample is achieved.In this embodiment, when the receiver section of the probe is detectinga signal, the distance from the probe to the sample can be known. Thisembodiment may lend itself to greater ease of analysis and probecalibration.

For many applications, however, the bistatic configuration is notuseful. For example, contours to the sample may cause shadowing of theresponse from the surface of the sample to the receiver, or may causethe overlap of the receiver line of sight and the illumination line ofsight to fall off of the surface. The monostatic optical design mayovercome these problems. It is furthermore understood that misalignmentproblems can be overcome by use of a monostatic optical configuration.Additionally, if the monostatic optical configuration is also confocal,the optical receiver will collect only the light from the illuminatedregion on the sample.

In one embodiment of a monostatic device, the illuminating beam of lightmay be transmitted through a beamsplitter before it interacts with thesample. The light emitted by the sample returns to the beamsplitter,where it is reflected toward a receiver system in the device. If theilluminating excitation beam and the returned emission from the sampleoccupy different regions of the electromagnetic spectrum, thebeamsplitter can be a dichroic mirror, with high transmission at theexcitation wavelengths and high reflectivity at the sample emissionwavelengths. This offers the possibility for high efficiency of opticalthroughput in the device. If, however, the spectral regions for theexcitation and emission beams have significant overlap, the dichroicmirror cannot be used, and significant losses of optical signal canoccur. In the case where the excitation and emission spectral regionsare identical, the optimum beamsplitter will transmit only 50% of theexcitation signal, and will reflect only 50% of the returned signalemitted by the sample. The overall efficiency of such a device is only25%.

Another limitation of the use of a beamsplitter in the path of theexcitation and emission beams is the possibility that light can bedirectly scattered from the illumination side to the receiver side ofthe probe without interaction with the sample. This can create largeoptical signals containing no information about the sample.

It is understood in the art that probes are available for multispectralimaging of a sample. A probe may comprise a housing and beam splittingapparatus within the housing, designed for imaging. Such a probe may notaddress the problem of scattering from the beam splitting surface andthe level of interference this scatter will cause.

It is well known in the art that optical interrogation of samples maypermanently alter the nature of the sample as a result of themeasurement. Laser-induced fluorescence studies of samples, for example,temporarily alter the physical nature of the molecules in the sample.This alteration produces molecules in excited energy states thatliberate optical radiation as they relax to the more favorable groundenergy state. Chemical and biological changes in specific samples canalso be created to liberate an optical response from the sample. Anexample of a permanent change in the sample is seen in laser breakdownspectroscopy, where a portion of the surface of the sample is ablated bythe intense laser beam. The ablated material is in the form of anexcited plasma that liberates light distinctive of the composition ofthe sample.

While some changes in the physical, chemical, or biological condition ofthe sample can be important for creating a response to the illumination,certain other changes in the sample that may be caused by an opticalsystem or a probe may interfere with the desired measurement. Forexample, it is known from spectroscopic studies of in-vivo tissue thathemoglobin content can have diagnostic significance. Optical probes thatcontact the tissue can alter the flow of blood to the tissue, therebyaltering the hemoglobin spectral feature. Such changes in samplecharacteristics adversely affect the ability of the optical device tomeasure the sample characteristics correctly. Contact of the probe withthe target tissue may cause other relevant changes in the signalsemitted from the tissue following illumination.

Probes in the art are known that identify tissue which is suspected ofbeing physiologically changed as a result of pre-cancerous or cancerousactivity by contacting the tissue, using separate optical fibers fortransmitting the excitation light and receiving the emitted light, orusing other conduits to direct heat, electrical, sound, or magneticenergy towards a target tissue. These devices rely upon contact with thetissues to derive their data, and do not embody a non-contact system foridentifying tissue abnormalities.

Non-contact optical probes may be configured so they do not alter asample in the same way as contact probes. Non-contact methods areparticularly attractive in medical in-vivo diagnostic instrumentationbecause they do not perturb the tissue being investigated and becausethey do not carry the risk of contamination of the measurement site.However, non-contact probes can suffer from other limitations, mostnotably problems with alignment and focus. For proper operation, the twomain components to the probe, namely the illumination section and thereceiving section, must be aligned to the same location on the sample,and both must be in focus at the same time. Non-contact probes are knownin the art that comprise systems for confocal illumination of a surfacewithout including an apparatus for eliminating the scattered light frombeing transmitted from the transmitter portion to the receiver portiondirectly in the probe when a monostatic arrangement is used.

Therefore, there remains a need in the art for a confocal optical systemthat optimizes the retrieval of the emitted light from a sample afterillumination in a monostatic configuration. There exists a further needto embody this system in a probe that does not require contact with thesample being illuminated. There exists an additional need for anon-contact probe that can measure the distance to the target tissue andthat is adapted for optimal positioning with respect to the targettissue. No system exists presently in the art that permits an accuratenon-contact technique of monostatic illumination of a sample without thepotential of interference from scattered light from the components ofthe illumination probe. Additionally, when such optical probes are usedin confined spaces, as is the case when illuminating in-vivo cervicaltissue, the optical probe often obscures the common viewing of thetissue. Therefore, there is a further need to provide supplementalability to view the target tissue during placement of the probe andduring optical illumination.

SUMMARY OF THE INVENTION

It is desirable that an optical probe be provided for identifying lightemission responses from a sample subjected to illumination. It isfurther desirable that the optical probe not interfere withphysiological or morphological characteristics of the sample beingexamined, nor that the probe impede the ability of an optical system todetect identifying features of the response from the sample. If, forexample, a desired response includes spectroscopic information (lightintensity as a function of wavelength), the probe will advantageously beconstructed so it will not contribute excessive spectroscopic detail tothe signal. Similarly, if a desired response from the sample includesspatially related data, the optical probe will advantageously providesufficient imaging quality to permit the identification of spatialcomponents of the response.

In one embodiment, the present invention may comprise a probe bearingone or a plurality of lenses or mirrors for the purpose of bringing theilluminating light to a focus on the surface of the sample. Thetransmitting optics may occupy the center region of a cylindricalgeometry. Surrounding the transmitter optics in this embodiment may bean annular optical arrangement for receiving emitted light from thesample. According to this embodiment, the emitted light returned to theprobe passes through an optical system containing components differentfrom the optical components used to form and direct the illuminatingbeam toward the sample, while remaining aligned to the same line ofsight as the illuminating beam.

In one embodiment, the annular receiver optical system may be designedso that it accepts light emitted from the focused spot on the sampledefined by the location of the illumination focal point. The emittedlight from the sample collected by the probe receiver optics may then bebrought to a focus elsewhere in the system for detection of fortransport to a means of detection. This point of focus in the probe maybe the active element of a detector, or may be the face of a fiber orfiber bundle, designed to conduct the light to another location in thedevice where the detection will take place. The terms receiving andcollecting optics, as used herein, are understood to be interchangeable.Furthermore, the receiving optics are understood to collect, to receiveand to retrieve light: all of the foregoing three terms areinterchangeable, as they are used herein.

Because no single optical component is used in both the transmitter andthe receiver portions of the device, the opportunity for scatteredradiation from the illuminating source to enter the receiver portion ofthe device without first having interacted with the sample is greatlydiminished, as compared to the technique of using a beamsplitter withinthe optical path. Care must be taken to account for light reflected fromoptical surfaces such as lens surfaces. This form of stray light cancontaminate the measurement of the surface by passing directly from theillumination portion to the receiver portion of the probe withoutinteracting with the sample. Practitioners of the art are familiar withbaffles and stops to prevent this level of stray light contamination inthe final signal.

In a particular embodiment, the sample being interrogated by the opticalbeam is in-vivo tissue. It is known in the art that when tissue isilluminated at a spatially limited point (e.g. 1-mm diameter spot) by acollimated beam of light, the emitted response from the tissue is in twoparts. The first is a specular reflection from the surface, and isgoverned by Fresnel reflection created by the change in index ofrefraction between the air and the tissue. The second is a diffusedreflection caused by the entrance of the light into the tissue where itmigrates randomly before escaping the surface. It is known that thisdiffused reflection can occur over a wide angle from the surface. Insome cases, this diffused component is modeled as having equal amountsof light in all angles measured from the perpendicular to the surface.

When the placement of the probe is critical to the quality of themeasurement, and when the use of the probe is in confined spaces such asis the case when viewing in-vivo cervical tissue, it is useful toaugment the operator's viewing ability of the target. This may beaccomplished by means of a video camera mounted directly in the probe.The optical system for the direction and focus of the illuminating beamcan also serve as the optical system to create an image of the surfaceof the sample for the video camera.

In one aspect, the present invention provides a system for examining asample that includes an optical probe with a plurality of optical fiberscapable of illuminating a sample, and a substantially monostatic,substantially confocal optical system comprising transmitting optics toilluminate a sample and receiving optics to collect light emitted fromthe sample. In certain embodiments, the system may include a reflectiveoptical component or a refractive optical components. The system mayfurther comprise an optical system that focuses illuminating light on asurface of the sample and that collects light emitted from the focuspoint. In one embodiment, the receiving optics of the system may beconfigured circumferentially around a light path followed by theilluminating light. In one embodiment, the system may provide a scannerthat directs illuminating light towards the sample by sequentiallyilluminating individual optical fibers in a preselected pattern, such asa rectilinear array or a hexagonal pattern. The illuminating light mayinclude a pulsed laser or a nitrogen laser and the emitted light mayinclude fluorescence or Raman scattered light. The illuminating lightmay include broadband light, for example from a Xenon lamp, and theemitted light may include elastic backscattered light.

In one aspect, the present invention provides a system for determining acharacteristic of a sample that includes an optical probe formonostatic, confocal examination of the sample; an optics system thatincludes transmitting optics to focus an illuminating light on thesample and receiving optics to collect light emitted from the sample; ameasuring system that produces quantitative data related to the lightemitted from the sample; and a processor that processes the quantitativedata to determine the characteristic of the sample. The system mayfurther include a video system to display an image of the surface of thesample. The -system may further include a position sensor to determinethe position of the optical probe in relation to the sample. Theposition sensor may provide a focusing image that is projected upon asurface of the sample, whereby the position of the optical probe inrelation is determined by the clarity of focus of the focusing image.

In another aspect, the present invention provides an optical probesystem for the monostatic, confocal examination of a sample, includingan optical probe, a light source that produces an illuminating light,transmitting optics that focus the light on a sample, collecting opticsarranged substantially as an annulus surrounding a light path for theilluminating light that collect light emitted from the sample, and aconnecting circuit that transmits electromagnetic energy related to theemitted light to a processor for further processing. The system mayinclude a scanning system that sequentially illuminates a plurality ofoptical fibers to pass a point of illumination over the surface of thesample in a preselected pattern. The system may further include a videochannel for viewing the surface of the sample and for determining thelocation of the probe relative to the sample. The video channel mayshare an optical path with the illuminating light. The system mayinclude a video camera dimensionally adapted for mounting on an opticalprobe.

In another aspect, the present invention provides a method for examininga sample, including the steps of providing a monostatic, confocaloptical probe with transmitting optics and collecting optics wherein thecollecting optics are disposed around a circumference of a light pathfor transmitting an illuminating light towards the sample; determiningan optimal position for the probe in relation to the sample and placingthe probe in that position; illuminating the sample with a light beamtransmitted through the transmitting optics; and collecting lightemitted from thesample as a result of the illumination. The method mayinclude the step of processing electromagnetic energy related to thecollected light to derive data related thereto. The method may furtherinclude creating a graphic image to represent the data related to thelight collected. The method may include directing a focusing imagetowards the sample to determine the optimal position of the probe inrelation to the sample.

In another aspect, the present invention provides a method fordiagnosing a medical condition, comprising the steps of providing amonostatic, confocal optical probe comprising transmitting optics andcollecting optics wherein the collecting optics are disposed around acircumference of a light path for transmitting an illuminating lighttoward a body tissue; illuminating the body tissue; collecting lightemitted from the body tissue; measuring a set of data related to thelight collected from the body tissue; and diagnosing from the set ofdata the medical condition. The method may further include processingthe set of data with a processor. The method may further includecreating a graphical image that represents the set of data.

In another aspect, the present invention provides a method of treating amedical condition, including the steps of providing a monostatic,confocal optical probe capable of illuminating a body tissue and capableof collecting therefrom emitted light, illuminating the body tissue,collecting emitted light from the body tissue, measuring a set of datarelated to the light emitted from the body tissue, diagnosing from theset of data the medical condition, formulating a treatment plan based ona diagnosis of the medical condition, and treating the medical conditionaccording to the treatment plan.

In another aspect, the present invention provides a system for examininga body tissue, including an optical probe that directs an illuminatinglight towards the body tissue and that collects light emitted from thebody tissue; a substantially monostatic, substantially confocal opticalsystem comprising transmitting optics that focus the illuminating lighton the body tissue and receiving optics that collect light emitted fromthe body tissue; and a measuring system that produces quantitative datarelated to the light emitted from the body tissue. In one embodiment,the body tissue is the cervix uteri.

In another aspect, the present invention provides a system forevaluating a medical condition in a patient, including an optical probethat directs an illuminating light towards a body tissue and thatcollects light emitted from the body tissue; a substantially monostatic,substantially confocal optical system comprising transmitting opticsthat focus the illuminating light on the body tissue and receivingoptics that collect light emitted from the body tissue; a measuringsystem that produces quantitative data related to the light emitted fromthe body tissue; a processor for processing quantitative data to derivediagnostic data related to the medical condition of the patient; and adatabase wherein the diagnostic data related to the medical condition ofthe patient may be stored. In one embodiment, the database may alsostore the patient's medical record. In another embodiment, the systemmay include a tracker to record procedure data from the procedurewherein the system is used to evaluate the medical condition of thepatient. The tracker may store procedure data in the database. Thedatabase may further comprise billing information, and the system mayfurther relate billing information to the procedure data.

In another aspect, the present invention provides a method fordelivering a health care service, including the steps of storing amedical record of a patient in a database; collecting billinginformation related to the patient; evaluating a body tissue of thepatient with an optical system comprising an optical probe formonostatic, confocal examination of the body tissue using anilluminating light focused on the body tissue by transmitting optics andusing a collection system for retrieving light emitted by the bodytissue after illumination; processing the light emitted by the bodytissue to produce a diagnosis of a medical condition of the patient;entering the diagnosis in the medical record; and relating the diagnosisto the billing information to generate a bill. The method may furtherinclude the step of recording procedure data in the database for theprocedure of evaluating the body tissue. The method may further includethe step of relating the procedure data to the billing information togenerate a second bill for the health care service.

These and other features of the systems and methods of the presentinvention will become more readily apparent to those skilled in the artfrom the following detailed description of certain illustrative orpreferred embodiments thereof.

BRIEF DESCRIPTION OF THE FIGURES

For a more complete understanding of the nature and objects of theinvention, reference should be made to the following detaileddescription and accompanying drawings.

FIG. 1 provides a schematic diagram of an embodiment of an optical probe

FIG. 2 provides a schematic diagram of an embodiment of an optical probeemploying a laser for illumination.

FIG. 3 provides a schematic diagram of an embodiment of an optical probewherein the optical transmission and receiving paths are substantiallyequal.

FIG. 4 provides a schematic diagram of an embodiment of an optical probeshowing the presence of a turning mirror.

FIG. 5 provides a schematic diagram of an embodiment of an optical probeshowing the presence of two turning mirrors.

FIG. 6 provides a functional block diagram of a system for examining asample according to the present invention.

The foregoing and other objects, features and advantages of the presentinvention will be apparent from the following more particulardescription of illustrative embodiments of the invention, as illustratedby the accompanying figures in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis being placed instead upon illustratingthe principles of the invention.

DETAILED DESCRIPTION OF THE FIGURES

FIG. 1 shows a schematic cross-section of one embodiment of the opticalprobe 10 according the invention. A housing 14 having a proximal and adistal end is shown in this figure as enclosing the optical components.The distal end of the housing may be most remote from the operator orclosest to the target sample. While a housing 14 is shown in theembodiment depicted in FIG. 1, it is understood that an optical probemay be constructed according to these systems and methods wherein theoptical elements are not enclosed as a single housing. Otherarrangements combining elements for illuminating a sample and forcollecting light from the sample after its illumination may be readilyenvisioned by practitioners of ordinary skill in these arts, and certainof these arrangements are depicted in the embodiments illustrated in thefollowing figures.

FIG. 1 further shows refractive optics 15 internal to the probe forminga focus 16 of the illuminating light on the surface of the sample 18.The source of the illuminating light 12 may be the end of a fiber ofdiameter d and numerical aperture Na_(f). The diameter of the opticalelements and the placement of these elements relative to the end of thefiber are such that the light exiting the fiber is entirely collected bythe optical elements and directed to a focal point of diameter D on thesurface of the sample. The measure of D may be greater than, less than,or equal to the measure of d. The magnification of the illuminatingoptics is then said to be D/d. Other configurations of illuminationsystems may be envisioned by or familiar to ordinarily skilledpractitioners of these arts.

In this and all other figures of this disclosure, the optical system forthe illumination and receiving sections of the probe are each drawn, forillustrative purposes, as comprising a single lens. It is understoodthat embodiments of the probe may be constructed that bear collectionsor arrays of lenses configured for different purposes, and that theseadditional embodiments are specifically contemplated by the systems andmethods of the present invention.

While the light paths shown in FIG. 1 illustrate a single beam ofilluminating light, it is understood that a plurality of optical fibersproviding illuminating light may be illuminated in a sequential mannerto create a pattern of illuminating light directed to the target. Theorder in which the fibers are illuminated may be predetermined in orderto form a particularly advantageous pattern of illumination on thetarget. A scanning system may be included in these systems and methodsto direct the sequence of fiber illumination. Patterns of illuminationand sequencing of optical fibers to attain those patterns may be readilyenvisioned by those of ordinary skill in the relevant arts.

In FIG. 1, the receiver optics 20 is shown to be shaped in an annularfashion around the central illuminating optical path. While an annulusis depicted here, practitioners of ordinary skill in the art willappreciate that any geometric shape arranging the receiver opticscircumferentially around a central illuminating axis may be substitutedas embodiments falling within the scope of the present invention. In theillustrated embodiment, the optic axis for the receiver optics is thesame as the optic axis for the illuminating optics. A baffle or barrier24 may optically separate the illuminating section of the optics fromthe receiving section. This barrier may prevent stray light fromentering the receiver optics 20 directly from the illuminating portionof the probe.

In the embodiment illustrated in FIG. 1, the component of theilluminating light that is specularly reflected (i.e., wherein the angleof reflection equals the angle of incidence) from the surface of thesample 18 is not directed into the receiver section when the distalsurface of the probe is normal to the line of sight (or symmetry axis)of the probe. This specular component of the reflection may be collectedby the illuminating optics, rather than the receiver optics. As aresult, the specular component may not be detected by the detector.Diffusely reflected light from the surface, however, can occur at anglesother than the angle of incidence. Thus, a portion of this diffuselyreflected light may be collected by the annular optical receiver opticsand brought to a focus within the body of the probe

Other spectroscopic methods such as fluorescence and Raman spectroscopybenefit from the fact that the specularly reflected component of theexcitation beam is not collected by the receiver optics 20. In thefluorescence technique, for example, a laser may be used to illuminatethe sample at a specific wavelength. The light emitted from the sampleas a result of the excitation by the laser beam may be produced byphysical or chemical components of the sample. In one embodiment,emitted light may be observed at wavelengths longer than the wavelengthof the excitation beam, but shorter wavelengths can also beinvestigated. The specularly reflected laser beam tends to be moreintense than the fluorescence signal, and may constitute unwantedradiation in fluorescence experiments. An embodiment of a probe asillustrated in FIG. 1 may significantly reduce the amount of specularlyreflected laser light entering the receiver portion, thus reducing theunwanted signal generated by the laser.

It is understood that fluorescence emitted by an illuminated sample doesnot retain the degree of collimation and wavelength purity of theilluminating laser beam. In most cases, fluorescence can be consideredto be nearly isotropic, that is, that all directions for thefluorescence emission are equally probable. Therefore, fluorescence froma sample may be similar to diffuse reflectance, with light propagatinginto all possible angles from the surface. Also, the intensity of thefluorescence emitted from most samples can be very weak compared to theilluminating beam. The receiver section of the probe may thus beadvantageously designed to collect a maximum amount of the emitted lightfrom the sample in fluorescence applications. This may be accomplishedby making the annular receiver area as large as possible, and byselecting optical coatings for the components that match the opticalbandwidth of the fluorescence signal.

FIG. 2 depicts an embodiment wherein the illuminating laser beam issufficiently well collimated that precise illuminating optics may becomeoptional. In this figure, a laser beam 30 passes straight through theprobe without alteration by an optical system. In the depictedembodiment, the illuminating portion of the probe occupies the areabetween the two optical barriers 24 that separate the illuminatingportion from the receiver optics 20. Use of a well collimated laserreduces the area occupied by the illuminating portion of the probe,creating a greater overall area for the receiver optics 20. Anembodiment like that shown in FIG. 2 is particularly well adapted forfluorescence studies of samples.

Information concerning the physical, chemical, or biological nature of asample can be communicated through the diffusely reflected portion ofthe reflected light from the surface. This is especially true ofbiological tissue, where a portion of the illuminating light enters thetissue and undergoes scattering and absorption before exiting thetissue. Through this process, the propagation direction of the light israndomized, becoming diffusely reflected rather than specularlyreflected. In addition, information regarding the sample is imparted tothe light beam, especially through the spectrum of the diffuselyreflected beam. Diffuse reflectance from other samples such as soils,chemical powders, polymer surfaces, textiles, etc. contains informationon the chemical composition of the sample.

For some applications of the optical probe, it may be advantageous tobalance the amount of light delivered to the sample and the amount oflight collected by the receiver portion. This balancing may bedesirable, for example, when a broadband white light is used tointerrogate the sample by creating a diffused reflectance spectrum ofthe sample. In such a situation, a useful design may provide an area ofthe illumination optics and an area of the receiving optics that areequal. For example, if the overall probe diameter is P, the diameter ofthe inner portion (the illuminating section in this embodiment) will beP/2 to achieve the equal areas in the receiver and illuminationsections. An embodiment showing these features is illustrated in FIG. 3.

FIG. 3 depicts an embodiment wherein the light collected by the receiverportion of the probe may be brought to a focus 38 at some distance fromthe collecting optics. In the illustrated embodiment, the location ofthis focus 38 is within the body of the probe. To avoid overlap of thispoint with the source of illuminating light 12, a number of options maybe available that are consistent with the monostatic design. In oneembodiment, the focal length of the receiving optics 20 may be longerthan the focal length of the illumination optics. This will cause thelocation of the receiver focal spot 38 to fall at a greater distancefrom the optical system than the distance of the source from the sameoptical system. The result is the ability of the received light to passaround the location of the source and form a focal spot. This focal spot38 may advantageously coincide with the location of a detecting element.Alternatively, the focal spot 38 may coincide with the location of afiber end or a fiber bundle end adapted for transmitting received lightto another location for detection. Similarly; it could be the locationof a fiber end or fiber bundle end designed to transmit the receivedlight to another location for detection. It is understood that any typeof optical transducer, photodetector or phototransistor may be suitablefor positioning at or near the focal spot to collect, measure orgenerate a signal in response to the focused light.

Because the receiver optical element or elements are arranged in acircumferential array around the illuminating beam in the depictedembodiment, the central portion of the conical beam coming to a focus,38, is obscured. This may allow the received beam to pass around theilluminating source 12 without losses.

FIG. 4 depicts an alternative embodiment not comprising the use ofunequal focusing dimensions. In the illustrated embodiment, a smallturning mirror 50 can be inserted into the illuminating beam path beforethe focusing lens 15 is encountered by the beam. This mirror 50 allowsthe illuminating source 12 to be placed away from the point at which thereceived light is brought to a focus 38 by the receiving lenses 24.

FIG. 5 depicts an embodiment wherein the operation of the optical probe10 may advantageously employ an angular design instead of a straightdesign. In the depicted embodiment, a mirror 50 can be used to deflectthe illuminating light from illuminating source 12, and a mirror 55 canbe used to deflect the received light and direct it to a focus 38.

FIG. 6 shows a functional block diagram of an embodiment of a systemaccording to the present invention. This figure shows an optical probe100 directed towards a sample 102. A distance x exists between thedistal end of the probe 100 and the sample 102. In one embodiment, theoptical probe 100 may contain all of the components necessary togenerate the desired illuminating light and to convert the receivedlight from the sample into electrical signals. Such a probe may betermed self-contained. In another embodiment, the optical probe 100 mayreceive transmitted light from a console 108 to which it is operablyconnected, or may transmit light received within the optical probe 100to the console 108. Such a probe may be termed remote-operated.

If the optical fibers are used for transmitting light to and from theoptical probe 100, the generation of the illuminating light can takeplace in the console 108. This light is carried to the optical probe 100through the fibers within the connecting circuit 104, where it is thenformed by the optics in the probe 100 to come to a focus on the sample102. Similarly, when optical fibers are used, the collected light fromthe sample 102 can be focused on the end of a fiber or bundle of fibersand transmitted to the console 108 for detection. If the connection tothe console 108 is through electrical wires only, the generation of theilluminating light and the detection of the light emitted by the sample102 must be done in the probe 100.

A remote-operated probe, furthermore, may be directed in threedimensional space via signals transmitted from an operator who directsthe positioning of the optical probe 100 with respect to the sample 102by inputting data into the console 108. The optical probe 100 isoperably connected to the console 108 by a connecting circuit 104, aconduit that may bear optical fibers, electrical wires or otherconductors adapted for transmitting electromechanical energy. Theconnecting circuit 104 may in some embodiments include systems forradiofrequency transmission. The connecting circuit 104 provides aconnection between the console 108 and the optical probe 100, so that anoperator may direct the functioning of the probe during the illuminationof the sample 102 and during the collection of light emitted by thesample 102.

This arrangement depicted in FIG. 6 allows for the direction of theprobe 100 to examine samples at a considerable distance from the site ofthe console 108 and the operator. An embodiment of a probe could bedirected, for example, to examine samples in locations inaccessible tohuman investigators. For example, a probe could be affixed to a cathetersystem for use within a body lumen or a channel bearing body fluids. Aprobe could also be adapted for insertion into small orifices such asEustachian tubes or nasopharyngeal or sinus passages. A probe could alsobe adapted for geological or industrial purposes, to be placed in smallcrevices or within structures. A probe could be adapted for use inhostile environments, including areas contaminated with infectiousagents, toxins or radiation, and including inhospitablemacroenvironments such as undersea use or extraterrestrial use. Otherembodiments of an optical probe according to these systems and methodsmay be devised that are suitable for various other environments andapplications, as will be envisioned by skilled practitioners in therelevant arts.

Optical instruments used to interrogate the physical, chemical, orbiological state of a sample may involve a method for deliveringspecific, known qualities of light to the sample, and collecting theresponse light from the sample for detection and analysis. In oneembodiment, an optical probe 100 may be incorporated in a system fordelivering the required light to the sample 102, and for collecting theresulting response for analysis. In certain embodiments, the opticalprobe 100 may be designed to be hand-held. It may furthermore bedesigned to withstand extremes in environmental conditions such astemperature or pressure. It may contain all of the required componentsnecessary to make the optical measurement of the sample, or it may beconnected to a console unit in which the requisite measurementcomponents are housed. The connecting circuit 104 may compriseelectrical, optical or other electromechanical components.

Data related to light emitted from the sample 102 may be manipulatedwithin a processor 110 so that other data sets related to the emittedlight may be obtained. Data may further be displayed in a graphicalformat on an image generator 114. The optical probe 100 may, in certainembodiments, bear a videocamera adapted for transmitting signals to avideo system 112. The video system 112 may be configured to producedigital data related to the images of the sample 102 transmitted fromthe optical probe 100. These digital data may be transmitted to theimage generator 114 to be displayed graphically, or to be combined withother graphic representations to produce a composite graphical image.

In one practice of these methods, the optical probe 100 may be broughtinto proximity to the sample 102. Proper operating distance x from thesample may advantageously be established in a number of ways. In oneembodiment, the distance x from the sample 102 to the optical probe 100can be measured, or can be fixed using a rod of known length. If this isnot possible, however, other methods for determining the properoperating distance can be used.

In one embodiment, an optical method for distance control may be usedwherein a visible grid or array of multiple spots on the sample may begenerated from an auxiliary light source in the console or in the probe.According to this embodiment, the grid may be projected through theoptics in the probe onto the target. When the grid is in focus, theprobe 100 is understood to be at the correct distance x from the sample102.

Proper focus of the confocal device may be judged by the quality of thefocus presented in the video image, or it may be augmented by specificfocusing aids. An example of a focusing aid comprises a projected gridor series of spots on the target. In this example, gross motion of theprobe towards or away from the target will bring the grid or spots intosharp focus, as viewed through the video channel. Fine adjustment of thefocus can be made as in a camera, by the adjustment of the opticalsystem delivering and receiving the light.

In another embodiment, an array of visible spots may be generated on thesample 102 by illuminating fibers in a fiber bundle located in the probe100, using, for example, a small laser situated in the console or in theprobe. The pattern of fibers in the bundle may be brought to a focus onthe target sample 102 by the optics in the optical probe 100. Accordingto this embodiment, when the spots are all in focus, the probe 100 is inthe proper position relative to the sample 102. With a number of spotsdistributed over the surface of the sample 102, angular errors such astilt of the probe can be eliminated when the correct focus is set foreach of the spots.

Other methods for determining whether the probe 100 is situated at theproper distance x from the sample 102 will be readily apparent to thoseof ordinary skill in these arts. Technologies related to radar, sonar,ultrasound or GPS may be adapted in certain embodiments to themeasurement of the distance x between the probe 100 and the sample 102.

A video viewing capability may be useful to confirm proper focus of thesample and proper alignment of the probe to the sample. A video viewingcapability may be advantageously employed when the optical probe is usedin confining spaces, or where access to the probe during operation isdifficult or impossible. The video camera may furthermore permit theoperator to position the probe for proper focus in relation to thesample. Viewing the focusing grid or spots may be accomplished throughthe optical configuration of the probe 100, allowing an operator toconfirm the accuracy of the focus of the probe's optics upon the sample.This feature may be provided by means of a video camera mounted in theprobe 100.

In an alternate embodiment, a beam splitter (not shown) may be providedin the transmitting beam path to combine a video capability with thediagnostic capability of the probe. The beam splitting element may alignthe viewing direction with the direction of the illuminating beam beingtransmitted to the sample. When the combination of the video anddiagnostic functions in the probe occurs before the illuminating lightpasses through the beam-forming optics, it is possible to use the videoimage to determine proper focus of the illuminating beam on the sample.This can be done by directly viewing the illumination spots on thesample, if the illumination occurs within the band of visiblewavelengths. If this is not the case, an aid to focusing is provided bysupplying an illumination grid or series of spots in the form of anarray covering the area of the sample.

With the video camera sharing its optical path with the illuminatingportion of the probe, the generation of the focusing grid or spots maytake place in the receiver section of the device. That is, the receiveroptics may be used to project the focusing grid or spot array onto thesample. By thus using the receiver portion of the probe to create theillumination of the focusing spots, a measure of the receiver focus maybe provided along with the visual realization of the illuminating focusoffered by the video camera. Thus the location of the probe for optimumfocus of both the transmitting and receiving portions of the probe maybe determined.

In certain embodiments the probe 100 is suitable for examination of asample 102 that includes a body tissue. A body tissue may include an invivo or an ex vivo tissue sample. A body tissue may include any tissueof a living body, whether external or internal. Body tissues may beaccessed via endoscopes, probes, specula, open surgical techniques orany other method familiar to practitioners in the relevant arts. Otherapproaches to body tissues suitable for the present invention will beapparent to those of ordinary skill in the medical arts. The examinationof a body tissue may yield a diagnosis of a medical condition. A medicalcondition may comprise any physiological or pathological state ofrelevance to the health or well-being of a human subject. Medicalconditions include both normal and abnormal conditions, and furtherinclude an entire spectrum of abnormalities. Examples of medicalconditions include neoplasms, malignancies, dysplasias, inflammation,infection, endocrine disorders, metabolic disorders, vascularabnormalities, reparative processes, regenerative processes,degenerative processes and other conditions affecting the health orwell-being of the subject. Data related to the systems and methods ofthe present invention may be processed to yield information aboutmedical conditions and diagnoses. In one embodiment, data collected fromthe examination of a body tissue of a patient may be compared to knowndata profiles for known medical conditions or diagnoses, so that adiagnosis may be established for the patient. In another embodiment,normal and abnormal levels may be established for certain data points ordata sets, so that the presence or absence of disease may be establishedby comparing the data points or data sets obtained from the examinationof a patient's body tissue with the established parameters. Afterestablishing a diagnosis according to these systems and methods, thepresent invention further provides for the establishment of a treatmentplan based thereupon. The diagnosed medical condition may then betreated according to the treatment plan. According to these systems andmethods, data related to the examination of the patient may becorrelated with other data in the patient's medical record.

In another embodiment, the systems and methods of the present inventionmay collect data pertaining to the examination procedure itself. Thesystem according to the present invention may measure and recordinformation about the duration of the procedure, the amount of energy orother consumable supplies utilized to perform the procedure, the numberof measurements taken during the procedure, or any other features of theprocedure of significance. In one embodiment, the procedure and itsduration may be tallied and correlated with patient information so thatan appropriate bill for the service may be constructed. Billinginformation may be entered into a database that can then be accessed bythe system to produce a bill for the particular procedure. In certainembodiments, the billing information may include a diagnostic or aprocedural code for categorizing the procedure so that a bill bearingthis information may be generated that will then be associated with aschedule of predetermined fees. Diagnosis according to ICD-9 codes andprocedural terminology according to CPT codes are well-known in the art.Other codes or categories may be used for organizing a patient's billinginformation, so that each procedure according to these systems andmethods will generate an accurate bill. Billing information may differfrom one patient to the next according to the fee schedules for variousmanaged care organizations and third-party payors. In one embodiment,the systems and methods of the present information may comprise theentry of billing information for a particular patient into a database.The billing information may then be correlated with data about theprocedure itself or with data about the diagnosis produced in order togenerate an accurate bill. Although the embodiments described hereinrelate to the application of these systems and methods to the diagnosisand treatment of medical conditions and to the delivery of health careservices, it is understood that these systems and methods may bedirected to the examination of any target, and that these systems andmethods may furthermore be correlated with systems for recording datathat identifies characteristics of the target so that outcomes of theexamination may be usefully stored in relation to other data pertainingto the target.

While this invention has been particularly shown and described withreference to certain illustrated embodiments thereof, it will beunderstood by those skilled in the art that various changes in form anddetails may be made therein without departing from the scope of theinvention encompassed by the appended claims.

1-51. (canceled)
 52. An apparatus for examining a sample, comprising: anoptical probe capable of illuminating a sample; and a substantiallymonostatic, substantially confocal optical system comprisingtransmitting optics adapted to direct illumination upon the sample, andreceiving optics adapted to collect light emitted from the samplefollowing illumination thereof.
 53. The apparatus of claim 52, whereinthe illuminating optics are disposed around a circumference of a lightpath for receiving light emitted from the sample.
 54. The apparatus ofclaim 52, further comprising a barrier element adapted to inhibitscattered illumination from entering the receiving optics.
 55. Theapparatus of claim 52, wherein the apparatus is adapted to bringilluminating light to a focus point at a location in the sample, andwherein the apparatus is adapted to collect light emitted from thelocation as a result of illumination with the illuminating light. 56.The apparatus of claim 52, wherein the illuminating light is provided bya broadband source and the emitted light comprises backscattered light.57. The apparatus of claim 52, wherein the illuminating light isprovided by a laser and wherein the light emitted from the samplecomprises fluorescence.
 58. The apparatus of claim 57, wherein the laseris a Nd:YAG laser.
 59. A method for diagnosing a medical condition,comprising the steps of: providing a substantially monostatic,substantially confocal optical probe comprising transmitting optics andcollecting optics, wherein the transmitting optics are disposed around acircumference of a light path for receiving light emitted from a bodytissue; illuminating the body tissue; collecting light emitted from thebody tissue; measuring a set of data related to the collected light; anddiagnosing a medical condition using the set of data.
 60. An apparatusfor examining a sample comprising: an optical probe capable ofilluminating a sample; an optical system comprising transmitting opticsadapted to direct illumination upon the sample, wherein the illuminatinglight comprises broadband light, and receiving optics adapted to collectlight emitted from the sample following illumination thereof; and abarrier adapted to inhibit scattered illumination from entering thereceiving optics.
 61. The apparatus of claim 60, wherein the opticalsystem comprises a substantially monostatic, substantially confocaloptical system.
 62. The apparatus of claim 60, wherein the receivingoptics comprises components separate and distinct from the transmittingoptics.
 63. The apparatus of claim 60, wherein the receiving optics arearranged circumferentially around a light path for the illumination. 64.The apparatus of claim 60, wherein the illuminating optics are arrangedcircumferentially around a light path for receiving light emitted fromthe sample.
 65. The apparatus of claim 60, wherein the sample comprisescervical tissue.
 66. The apparatus of claim 60, further comprising asystem for obtaining video information of the sample.
 67. The apparatusof claim 66, wherein the video information is used for at least one offocusing the probe and positioning the probe.